Document Detail

GOAT induced ghrelin acylation regulates hedonic feeding.
MedLine Citation:
PMID:  22982020     Owner:  NLM     Status:  MEDLINE    
Ghrelin is an orexigenic hormone that regulates homeostatic and reward-related feeding behavior. Recent evidence indicates that acylation of ghrelin by the gut enzyme ghrelin O-acyl transferase (GOAT) is necessary to render ghrelin maximally active within its target tissues. Here we tested the hypothesis that GOAT activity modulates food motivation and food hedonics using behavioral pharmacology and mutant mice deficient for GOAT and the ghrelin receptor (GHSR). We evaluated operant responding following pharmacological administration of acyl-ghrelin and assessed the necessity of endogenous GOAT activity for operant responding in GOAT and GHSR-null mice. Hedonic-based feeding behavior also was examined in GOAT-KO and GHSR-null mice using a "Dessert Effect" protocol in which the intake of a palatable high fat diet "dessert" was assessed in calorically-sated mice. Pharmacological administration of acyl-ghrelin augmented operant responding; notably, this effect was dependent on intact GHSR signaling. GOAT-KO mice displayed attenuated operant responding and decreased hedonic feeding relative to controls. These behavioral results correlated with decreased expression of the orexin-1 receptor in reward-related brain regions in GOAT-KO mice. In summary, the ability of ghrelin to stimulate food motivation is dependent on intact GHSR signaling and modified by endogenous GOAT activity. Furthermore, GOAT activity is required for hedonic feeding behavior, an effect potentially mediated by forebrain orexin signaling. These data highlight the significance of the GOAT-ghrelin system for the mediation of food motivation and hedonic feeding.
J F Davis; M Perello; D L Choi; I J Magrisso; H Kirchner; P T Pfluger; M Tschoep; J M Zigman; S C Benoit
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-08
Journal Detail:
Title:  Hormones and behavior     Volume:  62     ISSN:  1095-6867     ISO Abbreviation:  Horm Behav     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-04-24     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  0217764     Medline TA:  Horm Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  598-604     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Psychiatry, Metabolic Diseases Institute, University of Cincinnati, OH, USA.
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MeSH Terms
Acylation / physiology
Acyltransferases / genetics,  metabolism,  physiology*
Appetite Regulation / drug effects,  genetics,  physiology
Blood Glucose / drug effects,  metabolism
Body Weight / drug effects,  physiology
Feeding Behavior / drug effects,  physiology*
Ghrelin / blood,  metabolism*,  pharmacology,  physiology
Intracellular Signaling Peptides and Proteins / blood,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Motivation / drug effects,  genetics,  physiology
Neuropeptides / blood,  metabolism
Grant Support
1R01DA024680-01/DA/NIDA NIH HHS; K08 DK068069/DK/NIDDK NIH HHS; K08DK068069-01A2/DK/NIDDK NIH HHS; R01 DA024680/DA/NIDA NIH HHS
Reg. No./Substance:
0/Blood Glucose; 0/Ghrelin; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/orexins; EC 2.3.-/Acyltransferases; EC 2.3.-/ghrelin O-acyltransferase, mouse

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